This is a compilation of issues, points, instructions, and pointers that have been raised in past reviews. It is not intended to be an outline or to be comprehensive.

WHY HAVE IRB REVIEW?

"The high research value of human biological materials does not override the rights of individuals to protect themselves from possible adverse consequences of the research use of such materials." (National Bioethics Advisory Commission Draft Report, p 124) http://www.scribd.com/doc/23891605/Nbac-Human-Part-Vol2

"Where identifying information exists, however, there must be an unambiguous system of protections to ensure that risks are minimized and that the sample' source's interests are protected."

History, Fear and Unmet Expectations – Many of these words are imbued with stigma.

Was consent given? For what? Was it documented? Is a sample form available? Would the donor be surprised to learn about your use of the specimen? Might the donor disagree with your access to or use of the specimen? Is consent waiver possible?

PRIVACY

Who knows who the donor was? Where is the code held? Who can break it? How and when? When is the code destroyed irreparably? Is the same anonymous, de-linked, de-identified?

RIGHTS

By what right has the sample passed from the donor to the acquirer to the user?

SOURCE OF REGULATORY REQUIREMENTS

You need to give the IRB enough information to know which regulations must be applied.

NIH / CHTN

45 CFR 46

Research" is defined as a "a systematic investigation ... designed to develop or contribute to generalizable knowledge".

"Human Subject" is defined as a "living individual about whom an investigator ... conducting research obtains: (1) or (2) identifiable private information. ...".

FDA

21 CFR 50 and 56

If samples are to be used to develop a product such as a diagnostic device the study should comply.

Many states have rules regarding protection of patient privacy. It is the responsibility of the site to know their specific state requirements.

Institution

Internal Rules / IRB policies

Many institutions have institutional and IRB rules about secondary use of diagnostic or pathologic specimens. Any acquirer from an institutional source should be sure that institutional rules have been followed.

International

ICH

PROTOCOL ISSUES TO BE CONSIDERED

Any complete protocol should address the circumstances under which the specimen was obtained, the trail of handling from the acquirer to the user and the purposes for which it will be used. Every protocol will, however, put emphasis on different areas. This is NOT intended to be applied as an outline. It makes a terrible outline.

A. INTRODUCTION There should be an overview describing what is being done and why. It should be in language accessible to all members of the IRB.

When the IRB reads the application, will they receive a coherent picture of what you want and why?

When you have written your application, consider an unbiased assessment from an uninvolved friend.

To do research is a privilege, not a right. It is not a scientists’ absolute right to have access to samples; it is a right limited by ethics, laws, public perception and common sense.

A simple overview should be given. It should include a purpose, rationale, parties involved, and control points in the handling of the sample plus some information on how this study fits into the larger scientific environment.

Design:

What is the goal of this study? Why is it being done?

What part of this study is E&I’s IRB being asked to review?

Acquisition only (Which, if any, IRB[s] were involved?)

Use only (Which, if any, IRB[s] will consider the acquisition?)

Both?

Risks

To individual donors

Is it "less than minimal risk"?

Were financial, privacy and economic risks considered too?

To the class that the individual is part of

Is there any possible stigma or financial risk?

How "identifiable" is the sample and any accompanying information

Benefit

To individual?

To the class that the individual is part of?

To the company? (basic vs. applied)

To science??

B. TISSUE ACQUISITION ISSUES An IRB needs assurance that the original acquisition of the tissue was ethical.

If an E&I approved investigator is getting the samples, our IRB should have a protocol, should review the consent document, and should understand the eventual use and any restrictions on that use. This will be the heart of your application.

If an E&I approved investigator is acquiring the sample from a secondary source, our IRB should be assured that the acquirer is IRB approved and that the consent purpose contemplated the secondary use. Information about the acquisition may or may not be available. If it is not available, other assurances and documentation of approval from the original IRB may suffice.

1. Why did the initial collection occur?

Diagnostic specimen - waste from pathology or reference lab

Specimen in private collection

Volunteer donors

Retained from subjects in a research study

Was the sample existing as of the date you submitted the protocol?

Pharmacogenetics

2. Consent (If the sample is from a repository you may need their assurances. If you are obtaining the sample, the consent form will need review.)

Process

coercion if in therapeutic setting?

coercion if employees?

Elements

Specificity of purpose of end user (broad or general)

Storage of consent form

location, confidentiality, access?

Ability to refuse

now or withdraw sample later?

Was sample donation an integral part of study participation?

Was refusal perceived as a real choice?

Restrictions on use? (critical point)

Did the donor limit use? (consider religious issues, purpose as explained to the donor, etc.)

Was future re-sale considered?

Was consent reviewed by an IRB - was it waived? was documentation waived?

Examples of language found in some consent forms with evaluation. The IRB considers consent form language in terms of lay understanding.

Sample Consent Form statements and Critiques:

Statement: Purpose: "to examine, to retain for science or education or to dispose of."

Critique: None of the three verbs include to give or to sell to an outsider.

Statement: "... will not be used for commercial purposes."

Critique: A commercial company is presumed to have a commercial purpose.

Statement: "... will not be sold ... “

Critique: A transaction that is solely to cover the costs of collection is considered a sale.

Statement: "... will not be used for any genetics research..."

Critique: This would include both basic and applied genetic research.

Statement: "... will be destroyed.”

Critique: This is clear. It cannot be used.

Statement: "... will be used by an outside drug or biotechnology company for their basic research which might, some day, produce a product..."

Critique: This is clear. It is likely it can be used.

3 Ownership and Financial issues

Compensation to donor subject

Compensation to collector

Compensation to handler

When does "ownership" transfer at each step?

Is someone donating so that others can profit?

Cost to donor. Is the donor paying for the testing?

4. Risks

Physical risks from donation

Loss of privacy

Financial risks if status became known

Insurance issues

Stigma in community

Employee status?

Information available to employee health or human resources?

Family relations

Feedback of information could alter family dynamics.

Biosafety

What is the protocol for sample analysis in the event of an accidental needle stick?

Is there any need to return to the donor?

5. Benefits

Direct medical impact

Knowledge without known action to take

Assist to community of which donor subject is a member?

6. Adherence to source institution rules

Name of institution

Institutional compliance

Documentation

Foreign country collection and use (and discussion of their rules from that era and now)

7. Involvement of middlemen

Need to see their source documentation regarding institutional commitment

How do they assure the basics are considered?

Differences by type of organization

private, for profit

not for profit (NCI)

C. THE SAMPLE ITSELF As various kinds of samples are viewed differently, the IRB must know about the types of samples being sought.

1. Population (similar to “eligibility” criteria and often on your requisition form)

Were there an accidental needle stick, would there be any return to the source?

Is demographic information in a small sample sufficient to identify one person?

5. Demographics - Information available

What information is attached or linked to the sample?

6. Packing and Shipping

Speed (freshness)

Safety

State laws for contaminated substances

7. Storage

Potential length of time in storage (changes of rules over years?)

How identified in storage?

How is the consented use or purpose linked to the sample?

Backup protection at storage area? Emergency energy back-up?

D. RESEARCH PROJECTS - END USE The IRB must be assured that the purpose is consistent with the donor's consent, that protections are continued and that use is consistent with "community" and "local" values.